Animal Health Trust, Suffolk, UK.
Department of Materials Science and Engineering, University of Sheffield, Sheffield, UK.
J Tissue Eng Regen Med. 2020 May;14(5):690-700. doi: 10.1002/term.3030. Epub 2020 Mar 23.
Tendon injuries are a common cause of morbidity in humans. They also occur frequently in horses, and the horse provides a relevant, large animal model in which to test novel therapies. To develop novel cell therapies that can aid tendon regeneration and reduce subsequent reinjury rates, the mechanisms that control tendon tissue regeneration and matrix remodelling need to be better understood. Although a range of chemical cues have been explored (growth factors, media etc.), the influence of the mechanical environment on tendon cell culture has yet to be fully elucidated. To mimic the in vivo environment, in this study, we have utilised a novel and affordable, custom-made bioreactor to apply a cyclical strain to tendon-like constructs generated in three-dimensional (3D) culture by equine tenocytes. Dynamic shear analysis (DSA), dynamic scanning calorimetry (DSC) and Fourier-transform infrared (FTIR) spectroscopy were used to determine the mechanical and chemical properties of the resulting tendon-like constructs. Our results demonstrate that equine tenocytes exposed to a 10% cyclical strain have an increased amount of collagen gel contraction after 7 and 8 days of culture compared with cells cultured in 3D in the absence of external strain. While all the tendon-like constructs have a very similar chemical composition to native tendon, the application of strain improves their mechanical properties. We envisage that these results will contribute towards the development of improved biomimetic artificial tendon models for the development of novel strategies for equine regenerative therapies.
肌腱损伤是人类发病率的一个常见原因。它们在马中也经常发生，马为测试新疗法提供了一个相关的大型动物模型。为了开发可以辅助肌腱再生和降低后续再损伤率的新型细胞疗法，需要更好地了解控制肌腱组织再生和基质重塑的机制。尽管已经探索了一系列化学线索（生长因子、培养基等），但肌腱细胞培养中机械环境的影响尚未得到充分阐明。为了模拟体内环境，在这项研究中，我们利用一种新颖且经济实惠的定制生物反应器，对在三维（3D）培养中由马腱细胞生成的类似肌腱的构建体施加周期性应变。动态剪切分析（DSA）、动态扫描量热法（DSC）和傅里叶变换红外（FTIR）光谱法用于确定所得类似肌腱的构建体的机械和化学性质。我们的结果表明，与在没有外部应变的情况下在 3D 中培养的细胞相比，暴露于 10%周期性应变的马腱细胞在培养 7 和 8 天后胶原凝胶收缩量增加。虽然所有类似肌腱的构建体的化学成分与天然肌腱非常相似，但应变的施加改善了它们的机械性能。我们设想这些结果将有助于开发改进的仿生人工肌腱模型，以开发马再生治疗的新策略。
